A Phase 3 interventional study of Upadacitinib and Adalimumab in Rheumatoid Arthritis, sponsored by AbbVie. Completed at 218 sites in 25 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-08-14.
Sponsored by AbbVie · Phase 3, Interventional, and Treatment
Rheumatoid Arthritis (RA) is a chronic inflammatory disease causing pain, stiffness, swelling and loss of joint function. This study will assess how safe and effective upadacitinib is in treating RA when compared to adalimumab in adult participants with inadequate response or intolerance to one TNF-inhibitor who are on a stable dose of methotrexate (MTX). Adverse events and change in disease activity will be assessed.
Upadacitinib is an approved drug for the treatment of RA. This study is double-blinded means that neither the participants nor the study doctors will know who will be given upadacitinib and who will be given adalimumab. Study doctors put the participants in 1 of the 2 groups, called treatment arms randomly, to receive either upadacitinib or adalimumab. There is 1 in 2 chance that participants will receive adalimumab. Each group consists of 2 periods. Approximately 480 participants diagnosed with RA will be enrolled in approximately 250 sites across the world.
Participants will receive the oral upadacitinib once daily and matching adalimumab placebo every other week, or the subcutaneous adalimumab every other week and matching upadacitinib placebo once daily during Period 1. Eligible participants will continue to receive same study treatment in Period 2 as assigned in Period 1 and will be followed for 30 days and 70 days.
There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, checking for side effects and completing questionnaires.
2,888 studies on the registry are indexed under Arthritis, Rheumatoid; 390 are open to participants now.
This study's enrollment of 487 is above the median of 94 across 1,984 interventional studies indexed under Arthritis, Rheumatoid.
Browse Arthritis, Rheumatoid studies →AbbVie is the lead sponsor of 953 studies on the registry; 136 are open to participants now.
Of its 350 completed or terminated interventional studies of FDA-regulated products, 210 (60%) have results posted.
Counted across the registry records on this site, refreshed daily.
On oral or parenteral methotrexate (MTX) therapy >= 3 consecutive months and on a stable prescription of 15 to 25 mg/week (or >= 10 mg/week in participants intolerant of MTX at doses >= 15 mg/week) for >= 4 weeks prior to the first dose of study drug. In addition, all participants should take a dietary supplement of folic acid or folinic acid throughout the study participation.
Meets both of the following disease activity criteria:
Exclusion Criteria:
Participants will receive upadacitinib once a day along with matching placebo for adalimumab at eow (every other week) in Period 1. Eligible participants will continue to receive same study treatment in Period 2 as assigned in Period 1.
Drug: Upadacitinib · Drug: Adalimumab Matching Placebo
Participants will receive adalimumab at eow (every other week) along with matching placebo for upadacitinib once a day in Period 1. Eligible participants will continue to receive same study treatment in Period 2 as assigned in Period 1.
Drug: Adalimumab · Drug: Upadacitinib Matching Placebo
Oral Tablets
Also known as: RINVOQ
Subcutaneous Injection
Also known as: Humira
Oral Tablets
Subcutaneous Injection
Percentage of Participants Achieving Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) <= 3.2
The DAS28-CRP is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (NRS), and high-sensitivity C-reactive protein (hsCRP; in mg/L). Scores on the DAS28-CRP range from 0 to approximately 10, where higher scores indicate more disease activity. Low Disease Activity (LDA) based on DAS28 (CRP) is defined as achieving a DAS28 (CRP) of less than or equal to 3.2.
Time frame: Week 12
Number of Participants with Adverse Events
An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not the event is considered causally related to the use of the product.
Time frame: From first dose of study drug until 70 days following last dose of study drug (up to approximately 58 weeks)
Percentage of Participants Achieving American College of Rheumatology 50 % (ACR50) Response
Participants who met the following 3 conditions for improvement from baseline were classified as meeting the ACR50 response criteria: * 50% improvement in tender joint count (TJC68); * 50% improvement in swollen joint count (SJC66); and * 50% improvement in at least 3 of the 5 following parameters: * Physician's Global Assessment of Disease Activity measured on a Numerical Rating Scale of 0 to 10 (NRS) * Patient's Global Assessment of Disease Activity (NRS) * Patient's Assessment of Pain (NRS) * Health Assessment Questionnaire - Disability Index (HAQ-DI) * High-sensitivity C-reactive protein (hsCRP).
Time frame: Week 12
Percentage of Participants Achieving Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) < 2.6
The DAS28-CRP is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (NRS), and high-sensitivity C-reactive protein (hsCRP; in mg/L). Scores on the DAS28-CRP range from 0 to approximately 10, where higher scores indicate more disease activity. Clinical remission (CR) based on DAS28 (CRP) is defined as achieving a DAS28 (CRP) of less than 2.6.
Time frame: Week 12
Change from Baseline in Disease Activity Score 28 C-reactive Protein [DAS28-CRP])
The DAS28-CRP is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (NRS), and high-sensitivity C-reactive protein (hsCRP; in mg/L). Scores on the DAS28-CRP range from 0 to approximately 10, where higher scores indicate more disease activity.
Time frame: Week 12
Change from Baseline in Participants Assessment of Pain
Participants indicated their level of pain over the last 7 days using the Patient's Global Assessment Pain NRS. The range is 0 to 10 with no activity being indicated by 0 and severe activity by 10.
Time frame: Week 12
Change from Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) Score
The HAQ-DI assesses physical function in RA. The HAQ-DI score is the average of the highest score in each of eight categories. The total score is between 0-3.0, in 0.125 increments. Increasing scores indicate worse functioning with 0 indicating no functional impairment and 3 indicating complete impairment.
Time frame: Week 12
Showing the first 100 of 218 sites across 25 countries.
Plan to share: Yes — AbbVie is committed to responsible clinical trial data sharing. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information.
Supporting information: Study protocol, Sap
This study is completed, as verified in Aug 2026. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
AbbVie